PURPOSE: Platelet-derived growth factor (PDGF) promotes neuronal survival in experimental glaucoma and recruits glial cells that regulate synapses. We investigated the effects of intravitreal PDGF on the inflammatory milieu and retinal synapses in the presence of raised IOP. METHODS: Animals with laser-induced IOP elevation received intravitreal injections of either saline or 1.5 μg PDGF. At 7 days, a further intravitreal injection was administered so groups received "PDGF-saline" (n = 15), "PDGF-PDGF" (n = 13), or "saline-saline" (n = 20). Platelet-derived growth factor receptor activation was assessed after 2 weeks using Western blot for PI3 kinase. Immunohistochemistry was performed for markers of synapses in the inner plexiform layer (IPL): PSD-95, GluR1, SY38; RGCs: βIII-tubulin, and glial cells: Iba-1, CD45. Real-time quantitative polymerase chain reaction (qPCR) was performed for Arc, selp, MCP-1, IL-6, IL-10, and CX3CR1 (n = 13). RESULTS: A single injection of PDGF increased IPL synaptic density in high IOP eyes (PSD-95 = 8.65 ± 0.43, SY38 = 8.68 ± 0.51, GluR1 = 9.03 ± 0.60 puncta/μm3, P < 0.001) and expression of synaptic modulator Arc (6.92 ± 3.71-fold change/control, P < 0.05) in comparison with vehicle (PSD-95 = 4.59 ± 0.41, SY38 = 4.46 ± 0.38, GluR1 = 5.94 ± 0.50 puncta/μm3, Arc = 1.46 ± 0.31-fold/control). This was associated with more resident microglia (8.16 ± 1.34-fold change/control, P < 0.001) and infiltrating monocyte-derived macrophages in the retina as well as increased Selp expression (26.8 ± 14.12-fold change/control, P < 0.05). Optic nerve head (ONH) showed an increased microglia (saline = 1.44 ± 0.13 versus PDGF = 2.23 ± 0.18-fold change/control, P < 0.01) but not infiltrating macrophages. IL-10 expression was significantly increased in PDGF-treated eyes (5.43 ± 0.47-fold change/control, P < 0.05) relative to vehicle (2.51 ± 0.67-fold change/control). CONCLUSIONS: Platelet-derived growth factor increased microglial and monocyte-derived macrophage populations in the eye and protected intraretinal synapses from degeneration in our experimental glaucoma model.